Cellular and molecular mechanisms involved in T-cell-mediated autoimmunity affecting the retina are being studied in animal models of experimental autoimmune uveoretinitis (EAU). The questions are aimed at elucidating the mechanisms governing normal development and maintenance, as well as the pathological breakdown, of self-tolerance to retinal antigens. To address these questions, rats and mice are immunized with retina-derived antigens, or with synthetic peptides, representing fragments of these antigens, to induce EAU. Susceptibility to disease induction is being evaluated in various rodent strains of known genetic characteristics, in the hope of delineating the hereditary mechanisms that predispose to uveitis. Genetically altered (transgenic or "knockout") mice are used to evaluate the role of various components of the immune system in the immunopathogenesis of uveitis. In vivo functional T-cell lines and clones are developed from lymphoid organs of rats and mice immunized with uveitogenic ocular antigens. The functional properties and specific receptors of these cells are being studied with the aim of developing strategies for in vivo targeting of the autoimmune cells. Lastly, EAU in rats and mice serves as a template for the preclinical evaluation of new drugs and compounds as to their effects on the various stages of immunopathogenesis and final disease expression. The goals of these studies are to identify the immunogenetic factors predisposing to uveitic disease, learn about the pathogenic mechanisms involved, characterize the immunoreactive cells and their mediators, and use this knowledge of design novel and rational approaches to immunotherapy.